Molecular mechanisms of action of styrene toxicity in blood plasma and liver

Abstract

Styrene is an aromatic colorless hydrocarbon available in liquid form and highly volatile. In its pure form, it gives a sweet smell. The primary source of exposure in the environment is from plastic materials, rubber industries, packaging materials, insulations, and fiber glass and carpet industry. Natural sources of styrene include: few metabolites in plants which are transferred through food chain. The current study was designed to evaluate styrene toxicity, including: superoxide dismutase (SOD) and protein carbonyl, oxidative stress, glucose-6-phosphatase (G6Pase), glycogen phosphorylase (GP), and phosphoenolpyruvate carboxykinase (PEPCK) activities, adenosine triphosphate (ATP) to adenosine diphosphate (ADP) ratio, and changes in gene expressions such as glutamate dehydrogenase 1 (GLUD1), glucose transporter 2 (GLUT2), and glucokinase (GCK) in the rat liver tissue. For this purpose, styrene was dissolved in corn oil and was administered via gavage, at doses 250, 500, 1000, 1500, 2000, mg/kg/day per mL and control (corn oil) to each rat with one day off in a week, for 42 days. Plasma SOD and protein carbonyl of plasma were significantly up-regulated in 1000, 1500, and 2000 mg/kg/day styrene administrated groups (P < .001). In addition, styrene caused an increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) in the dose-dependent manners in liver tissue (P < .001). Furthermore, the ferrous reducing antioxidant power (FRAP) and total thiol molecules (TTM) in styrene-treated groups were significantly decreased in liver tissue (P < .001) with increasing doses. In treated rats, styrene significantly increased G6Pase activity (P < .001) and down-regulated GP activity (P < .001) as compared to the control group. The PEPCK activity was significantly raised in a dose-dependent manner (P < .001). The ATP/ADP ratio of live cells was significantly raised by increasing the dose (P < .001). There was significantly an up-regulation of GLUD1 and GCK at 2000 mg/kg group (P < .01) and a down-regulation for GLUT2 at the same dose. While in the rest of group, GLUT2 showed up-regulation of relative fold change. By targeting genes such as GLUD1, GLUT2, and GCK, disruption of hepatic gluconeogenesis, glycogenolysis, and insulin secretory functions are obvious. The present study illustrates that induction of oxidative stress followed by changes in G6Pase, GP, and PEPCK activities and the genes responsible for glucose metabolism are the mechanisms of styrene's action in the liver.

Styrene Oxide Caused Cell Cycle Arrest and Abolished Myogenic Differentiation of C2C12 Myoblasts

“…ese findings suggest that STO had an antiproliferative effect on C2C12 myoblasts by inducing cell cycle arrest in S-phase. e cause of antiproliferative effects of STO in myoblasts may be due to ROS production after STO exposure as previously reported [15]. Indeed, measurements of ROS after treatment with STO significantly increased the level of these free radicals (Figure 3(f )).…”

“…e toxic effects of STR and STO were mediated through an increasing level of reactive oxygen species leading to cellular oxidative stress [15,[18][19][20]. Also in our study, measurements of reactive oxygen species using H2DCFDA showed dose-dependent increases in ROS after treatment with STO (Figure 3(f )).…”

“…e lacks of cytotoxic effects of both STR and STO in this study are at variance with the others. Previously, it has been shown that treatment with STR caused an increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) of a rat liver in a dose-dependent manner [15]. Furthermore, in vitro study revealed that 50 μM STO induced DNA damages in human peripheral lymphocytes [16,17].…”

Microplastics induce transcriptional changes, immune response and behavioral alterations in adult zebrafish

“…With respect to the polymeric composition, polyethylene (PE), which is the polymer produced in the largest quantities worldwide 12 , represents the most abundant constituent of marine and freshwater MPs pollution 4,13,14 . Polystyrene (PS) is slightly less abundant than PE in the environment, but it has been suggested that its aromatic monomer, styrene, could cause acute toxicity and endocrine disruption 15,16 . MPs can be easily taken up by fish, and have been isolated from the gastrointestinal tract (GIT), gills, liver and muscle of wild specimens 17–19 .…”

Human plasma and liver concentrations of styrene estimated by combining a simple physiologically based pharmacokinetic model with rodent data

“…At present, epidemiologic evidence does not suggest a causal association between styrene and any forms of cancer in humans (Rueff et al, 2009). However, a vari-ety of food containers, drinking cups, and carpets fabricated from polystyrene or polystyrene-related plastics could contain styrene monomer (Withey, 1976;Niaz et al, 2017). To predict the toxicokinetics of volatile chemicals in mixtures, integrated physiologically based pharmacokinetic (PBPK) modelling has been proposed (Krishnan and Johanson, 2005;Ramsey and Andersen, 1984;Kirman et al, 2003).…”